Influence of extrinsic contribution on the macroscopic properties of hard and soft lead zirconate titanate ceramics

In this work, the contribution of the extrinsic effect to the macroscopic properties in soft and hard lead zirconate titanate ceramics is directly evaluated. Close to the room temperature, poled hard ceramics show an anomalous behavior, which is notably different from that of soft ceramics, not only in dielectric but also in piezoelectric and elastic responses. Hence, at room temperature their properties are thermally stable and the losses are unusually low. It is suggested that two mechanisms are present, with one mechanism inhibiting the other.Peer ReviewedPostprint (published version

Antibody-based immunotoxins for colorectal cancer therapy

Monoclonal antibodies (mAbs) are included among the treatment options for advanced colorectal cancer (CRC). However, while these mAbs effectively target cancer cells, they may have limited clinical activity. A strategy to improve their therapeutic potential is arming them with a toxic payload. Immunotoxins (ITX) combining the cell-killing ability of a toxin with the specificity of a mAb constitute a promising strategy for CRC therapy. However, several important challenges in optimizing ITX remain, including suboptimal pharmacokinetics and especially the immunogenicity of the toxin moiety. Nonetheless, ongoing research is working to solve these limitations and expand CRC patients’ therapeutic armory. In this review, we provide a comprehensive overview of targets and toxins employed in the design of ITX for CRC and highlight a wide selection of ITX tested in CRC patients as well as preclinical candidates. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

In vivo potential of recombinant granulysin against human melanoma

9-kDa granulysin is a protein expressed into the granules of human cytotoxic T lymphocytes (CTL) and natural killer (NK) cells. It has been shown to exert cytolysis on microbes and tumors. We showed previously that 9-kDa granulysin exerted cell death by apoptosis in vitro on hematological tumor cell lines and also on cells from B-cell chronic lymphocytic leukemia (B-CLL) patients. In addition, we have shown the anti-tumor efficiency of granulysin as a single agent in two in vivo models of human tumor development in athymic mice, the MDA-MB-231 mammary adenocarcinoma and the NCI-H929 multiple myeloma, without signs of overt secondary effects by itself. In this work, we have tested recombinant 9-kDa granulysin in an in vivo and especially aggressive model of melanoma development, xenografted UACC62 cells in athymic mice. Recombinant granulysin was administered once UACC62-derived tumors were detectable and it substantially retarded the in vivo development of this aggressive tumor. We could also detect apoptosis induction and increased NK cell infiltration inside granulysin-treated tumor tissues. These observations are especially interesting given the possibility of treating melanoma by intra-tumor injection

The Poor Survival among Pulmonary Tuberculosis Patients in Chiapas, Mexico: The Case of Los Altos Region

Objective. To analyse survival in patients with pulmonary tuberculosis (PTB) and factors associated with such survival. Design. Study of a cohort of patients aged over 14 years diagnosed with PTB from January 1, 1998 to July 31, 2005. During 2004–2006 a home visit was made to each patient and, during 2008-2009, they were visited again. During these visits a follow-up interview was administered; when the patient had died, a verbal autopsy was conducted with family members. Statistical analysis consisted of survival tests, Kaplan-Meier log-rank test and Cox regression. Results. Of 305 studied patients, 68 had died due to PTB by the time of the first evaluation, 237 were followed-up for a second evaluation, and 10 of them had died of PTB. According to the Cox regression, age (over 45 years) and treatment duration (under six months) were associated with a poorer survival. When treatment duration was excluded, the association between poorer survival with age persisted, whereas with having been treated via DOTS strategy, was barely significant. Conclusions. In the studied area it is necessary that patients receive a complete treatment scheme, and to give priority to patients aged over 45 years

Conjugation of the 9-kDa isoform of Granulysin with liposomes potentiates its cytotoxicity

Nine kDa granulysin (GRNLY) is a human cytolytic protein secreted by cytotoxic T lymphocytes (CTL) and NK cells of the immune system whose demonstrated physiological function is the elimination of bacteria and parasites. In previous studies by our group, the anti-tumor capacity of recombinant granulysin was demonstrated, both in vitro and in vivo. In the present work, we developed lipid nanoparticles whose surfaces can bind recombinant granulysin through the formation of a complex of coordination between the histidine tail of the protein and Ni2+ provided by a chelating lipid in the liposome composition and termed them LUV-GRNLY, for granulysin-bound large unilamellar vesicles. The objective of this formulation is to increase the granulysin concentration at the site of contact with the target cell and to increase the cytotoxicity of the administered dose. The results obtained in this work indicate that recombinant granulysin binds to the surface of the liposome with high efficiency and that its cytotoxicity is significantly increased when it is in association with liposomes. In addition, it has been demonstrated that the main mechanism of death induced by both granulysin and LUV-GRNLY is apoptosis. Jurkat-shBak cells are resistant to GRNLY and also to LUV-GRNLY, showing that LUV-GRNLY uses the mitochondrial apoptotic pathway to induce cell death. On the other hand, we show that LUV-GRNLY induces the expression of the pro-apoptotic members of the Bcl-2 family Bim and especially PUMA, although it also induced the expression of anti-apoptotic Bcl-xL. In conclusion, we demonstrate that binding of GRNLY to the surfaces of liposomes clearly augments its cytotoxic potential, with cell death executed mainly by the mitochondrial apoptotic pathway

La paleodieta de cinco especies de mamíferos herbívoros rancholabreanos de valsequillo (Puebla, México)

Through the use of the 13C/12C and 18O/16O isotopic relationships found at enamel and osteodentine, here it is inferred the diet and preferred habitat in which five extinct herbivore species from the Late Pleistocene of Valsequillo, Puebla, México. The horses, mammoths, and sloths showed a diet mainly based in C4, meanwhile the capybaraand gomphotheres were mixed C3/C4 feeders. The vegetation in which those animals lived was open with some trees, similar to the one proposed in other studies based in some macromammals species found in the locality.Usando las relaciones isotópicas de 13C/12C y 18O/16O presentes en el esmalte y la osteodentina, se infirió la dieta y el ambiente en el cual vivieron cinco especies extintas de herbívoros procedentes del Pleistoceno Tardío de Valsequillo, Puebla, México. Los caballos, los mamutes y el perezoso mostraban una dieta basada exclusivamente en plantas C4, mientras que el carpincho y los gonfoterios exhibían una dieta mixta C3/C4. El tipo de vegetación en el cual estos animales habitaron fue abierto con poca cobertura arbórea, misma que ha sido propuesta en otros estudios usando la presencia de algunas especies de micromamíferos encontradosen la zona

Resistance to DNA Damaging agents produced invasive phenotype of rat glioma cells-characterization of a new in vivo model

Chemoresistance and invasion properties are severe limitations to efficient glioma therapy. Therefore, development of glioma in vivo models that more accurately resemble the situation observed in patients emerges. Previously, we established RC6 rat glioma cell line resistant to DNA damaging agents including antiglioma approved therapies such as 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and temozolomide (TMZ). Herein, we evaluated the invasiveness of RC6 cells in vitro and in a new orthotopic animal model. For comparison, we used C6 cells from which RC6 cells originated. Differences in cell growth properties were assessed by real-time cell analyzer. Cells’ invasive potential in vitro was studied in fluorescently labeled gelatin and by formation of multicellular spheroids in hydrogel. For animal studies, fluorescently labeled cells were inoculated into adult male Wistar rat brains. Consecutive coronal and sagittal brain sections were analyzed 10 and 25 days post-inoculation, while rats’ behavior was recorded during three days in the open field test starting from 25th day post-inoculation. We demonstrated that development of chemoresistance induced invasive phenotype of RC6 cells with significant behavioral impediments implying usefulness of orthotopic RC6 glioma allograft in preclinical studies for the examination of new approaches to counteract both chemoresistance and invasion of glioma cells

Análisis de viabilidad de una empresa de lombricomposta a base de residuos orgánicos en Delicias, Chihuahua

En la actualidad, la contaminación y la problemática del medio ambiente son temas de mayor preocupación y por lo tanto más tratados. En México más de la mitad de la basura generada por una familia es orgánica y biodegradable y no se le está dando un tratamiento adecuado, pero la basura no solo se genera en casas particulares, sino también en establecimientos como restaurantes, escuelas, comercios, etc. Otro de los problemas actuales es el aumento en el uso y la demanda de fertilizantes químicos, los cuales si se usan excesiva y desequilibradamente causan problemas en el medio ambiente. Por esta razón se analizó la viabilidad de establecer una empresa de lombricomposta a base de residuos orgánicos para venta de humus como abono orgánico para plantas de jardín en Delicias, Chihuahua. Para desarrollar el proyecto se establecieron y cumplieron objetivos tales como determinar la demanda de la lombricomposta en Delicias mediante una investigación de mercado; determinar los recursos necesarios para establecer la empresa mediante un estudio técnico y realizar un análisis económico-financiero del establecimiento de la empresa a través del análisis de costos y mediante indicadores financieros como el VAN, TIR, y B/C. Los resultados fueron favorables, por lo que se determinó que es viable establecer una empresa de lombricomposta a base de residuos orgánicos en el municipio de Delicias, Chihuahua

Validity and factorial invariance of the social ecological model in explaining fruit intake in mexican school children

Objetivo: Estimar la bondad de ajuste del modelo Motivación- Habilidad-Oportunidad (MHO), a fin de evaluar la varianza observada en las preferencias para comer fruta y el consumo actual de fruta en niños escolares mexicanos; así como la invarianza factorial a través del género y tipo de población (urbana y semi-urbana) en la que residen los niños. Métodos: Se diseñó un modelo con siete constructos de un cuestionario validado que mide preferencias, habilidades cognitivas, actitudes, modelamiento, percepción de barreras, accesibilidad en la casa, accesibilidad en la escuela y la frecuencia de consumo de fruta. El cuestionario se aplicó en una muestra representativa de 1434 niños escolares de 10 a 12 años, de quinto y sexto grado de educación primaria, en un estudio transversal y ex post facto realizado en 2013 en seis ciudades del Estado de Chihuahua, México. Resultados: El modelo MHO mostró índices de ajuste adecuados y explicó el 39% de la varianza en las preferencias para comer fruta. La estructura del modelo muestra muy buena estabilidad en la estructura factorial y las dimensiones de la escala fueron equivalentes en las muestras analizadas. Conclusión: La modelización mediante ecuaciones estructurales muestra un modelo parsimonioso que, puede ser utilizado para explicar las variaciones en el consumo de fruta en niños escolares mexicanos de 10 a 12 años. La estructura del modelo fue estrictamente invariante y muestra evidencias de validación cruzada. Finalmente, se discuten las modificaciones requeridas para obtener un mejor ajuste de los datos en contextos escolares y las directrices a seguir en futras investigaciones.Objective: To test the goodness of fit of a Motivation- Ability-Opportunity model (MAO-model) to evaluate the observed variance in Mexican schoolchildren’s preferences to eat fruit and daily fruit intake; also to evaluate the factorial invariance across the gender and type of population (urban and semi-urban) in which children reside. Method: A model with seven constructs was designed from a validated questionnaire to assess preferences, cognitive abilities, attitude, modelling, perceived barriers, accessibility at school, accessibility at home, and fruit intake frequency. The instrument was administered in a representative sample of 1434 schoolchildren of 5th and 6th grade of primary school in a cross-sectional and ex post fact study conducted in 2013 in six cities of the State of Chihuahua, Mexico. Results: The goodness of fit indexes was adequate for the MAO-model and explained 39% of the variance in preference to eat fruit. The structure of the model showed very good factor structure stability and the dimensions of the scale were equivalent in the different samples analyzed. Conclusions: The model analyzed with structural equation modeling showed a parsimonious model that can be used to explain the variation in fruit intake of 10 to 12 year old Mexican schoolchildren. The structure of the model was strictly invariant in the different samples analyzed and showed evidence of cross validation. Finally, implications about the modification model to fit data from scholar settings and guidelines for future research are discussed